Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cytotoxicity of vincristine (VCR), beta-cytosine arabinoside (Ara-C), or adriamycin (ADRIA) in combination with 5-azacytidine (Aza-CR) to L1210 leukemia in vivo was measured to determine if schedule-dependent synergistic or antagonistic drug interaction occurred. Two dose levels of Aza-CR were studied (0.1 and 0.5 mg/mouse), and cytotoxicity was measured by the spleen colony assay. For the combination of Aza-CR plus VCR, cytotoxicity was essentially additive or antagonistic when VCR preceded Aza-CR and additive or synergistic when VCR followed Aza-CR. When Aza-CR was combined simultaneously with either Ara-C or ADRIA, cytotoxicity was markedly antagonistic but was additive if drugs were given sequentially. When Ara-C was given as a 24-hour infusion before Aza-CR, the resultant cell kill was antagonistic (although slightly greater than that obtained for Ara-C alone). However, antagonism was even more marked when Aza-CR was given before the 24-hour infusion of Ara-C; cell kill was less than that observed with Ara-CR alone. Synergistic cytotoxicity was observed only with VCR administered after a low dose of of Aza-CR. Therefore, scheduling of drugs in combination with Aza-CR may be critical in the determination of the antileukemic cytotoxic effects.
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PMID:Chemotherapy of L1210 leukemia with 5-azacytidine in combination with vincristine, adriamycin, or beta-cytosine arabinoside. 617 66

The use of sonicated phospholipid vesicles (liposomes) as carriers of methyl [5-(2-thienylcarbonyl)-1H-benzimidazol-2-yl] carbamate (Nocodazole), a water insoluble antimitotic compound active on mouse L1210 leukemia was investigated. Nocodazole was incorporated in dipalmitoyl-phosphatidylcholine: cholesterol: stearylamine (4:3:1) liposomes that were stable at room temperature for at least 48 hr. No drug leakage nor lipid exchange occurred after a 4 hr incubation at 37 degrees C with RPMI 1640 medium supplemented with 10% fetal calf serum. L1210 cells preincubated (2 x 10(6) cells/ml) at 37 degrees C for 3 hr with various concentrations of micronized Nocodazole or liposome-entrapped Nocodazole were injected i.p. into normal CDF1 mice (10(5) cells/mouse). Longest mean survival times and long-time survivors were observed in the group inoculated with L1210 cells preincubated with liposomes containing Nocodazole. CDF1 mice bearing i.p. or i.v. L1210 leukemia were treated i.p. on days 1, 5 and 9 with micronized or liposome-entrapped Nocodazole. Administration of this latter preparation induced a 50% increase in animal life span at the dosage (25 mg/kg/day) half the one required with the free compound (50 mg/kg/day). The present data indicate that enclosing Nocodazole, a water insoluble antimitotic compound, in liposomes results in an enhanced therapeutic activity against L1210 murine leukemia.
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PMID:Chemotherapeutic efficacy of Nocodazole encapsulated in liposomes on L1210 murine leukemia. 619 Feb 3

We studied the infectivity of endogenous ecotropic murine leukemia virus genomes contained in high-molecular-weight DNA prepared from virus-free cells of the AKR-2B line, and from RF, BALB/c, B6, and (BALB/c x B6)F(1) mouse embryo cells. When DNA prepared from virus-free AKR-2B cells was transfected into NIH-3T3 cells, no virus-positive cultures were observed, a result consistent with previous reports. However, when DNAs from virus-free AKR-2B cells or virus-free cells containing the RF/J or BALB/c ecotropic proviruses were transfected into chicken embryo cells that were then cocultivated with SC-1 (mouse) cells, virus-positive cultures were recovered. The specific infectivities of the AKR provirus(es) contained in virus-free cells and the molecularly cloned Akv-1 provirus were similar when chicken embryo cells were used as primary recipients. Virus-positive cultures were also observed when secondary mouse embryo cells were used as recipients for DNA from virus-free AKR-2B and RF/J cells. The transfected chicken embryo-SC-1 cultures produced XC-positive murine leukemia virus that is N-tropic. Virus-positive recipient cultures were observed 10- to 100-fold more frequently when AKR-2B DNA was used than when BALB/c DNA was used as the donor DNA. Our studies indicate that some nonexpressed ecotropic murine leukemia virus proviruses are activated upon transfection into chicken embryo cells. Such studies suggest that there are different factors governing the expression of murine leukemia virus after transfection into established cell lines (NIH-3T3) and into nonestablished secondary cultures (chicken and mouse).
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PMID:Activation of nonexpressed endogenous ecotropic murine leukemia virus by transfection of genomic DNA into embryo cells. 630 Apr 65

The 8.2-kilobase (kb) unintegrated circular DNA form of the FBJ murine leukemia virus (FBJ-MLV) was linearized by cleavage at the single HindIII site, molecularly cloned into bacteriophage Charon 30, and subsequently subcloned into pBR322 (pFBJ-MLV-1). Both FBJ-MLV virion RNA and pFBJ-MLV-1 DNA were used to investigate the arrangement of helper virus sequences in the FBJ murine osteosarcoma virus genome (FBJ-MSV) by heteroduplex formation with cloned FBJ-MSV proviral DNA. The results showed that the FBJ-MSV genome contained 0.8 kb of helper virus sequence at its 5' terminus and 0.98 kb at its 3' terminus. Approximately 6.8 kb of helper virus sequence had been deleted, and 1.7 kb of unrelated sequence was inserted into the FBJ-MSV genome. This substituted region contains v-fos, the transforming gene of FBJ-MSV. Using a probe specific for v-fos, we have cloned homologous sequences (c-fos) from mouse and human chromosomal DNA. Heteroduplex analysis of FBJ-MSV DNA with these recombinant clones showed that both the c-fos(mouse) and the c-fos(human) sequences hybridized to the entire 1.7-kb v-fos region. However, five regions of homology of 0.27, 0.26, 0.14, 0.5, and 0.5 kb were separated by four regions of nonhomology of 0.76, 0.55, 0.1, and 0.1 kb from 5' to 3' with respect to the FBJ-MSV genome. The size of these sequences showed striking similarity in both c-fos(mouse) and c-fos(human).
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PMID:Structure of the FBJ murine osteosarcoma virus genome: molecular cloning of its associated helper virus and the cellular homolog of the v-fos gene from mouse and human cells. 630 48

A family of recombinant mink cell focus-forming viruses (MCF) was derived by inoculation of NFS mice with a Friend murine leukemia virus, and their genomes were analyzed by RNase T1-resistant oligonucleotide fingerprinting. The viruses were obtained from the thymuses and spleens of preleukemic and leukemic animals and were evaluated for dualtropism and oncogenicity. All these isolates induced cytopathic foci on mink cells but could be classified into two groups based on their relative infectivities for SC-1 (mouse) or mink (ATCC CCL64) cells. One group of Friend MCFs (F-MCFs) (group I) exhibited approximately equal infectivities for SC-1 and mink cells, whereas a second group (group II) infected mink cells 1,000- to 10,000-fold more efficiently than SC-1 cells. Structural analyses of the F-MCFs revealed that group I and group II viruses correlated with recombination of Friend murine leukemia virus with two distinct, but closely related, endogenous NFS proviral sequences. No correlation was found between the type of F-MCF and the tissue of origin or the disease state of the animal. Furthermore, none of the F-MCF isolates were found to be oncogenic in NFS/N or AKR/J mice. F-MCFs of both groups underwent extensive substitution of ecotropic sequences, involving much of the gag and env genes of group I F-MCFs and most of the gag, pol, and env genes of group II F-MCFs. All F-MCF isolates retained the 3' terminal U3 region of Friend murine leukemia virus. Comparison of the RNAs of the F-MCFs with RNAs of MCFs derived from NFS.Akv-1 or NFS.Akv-2 mice indicated that the F-MCFs were derived from NFS proviral sequences which are distinct from the sequences contained in NFS.Akv MCF isolates. This result suggested that recombination with particular endogenous proviral sequences to generate MCFs may be highly specific for a given murine leukemia virus.
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PMID:Generation of mink cell focus-forming viruses by Friend murine leukemia virus: recombination with specific endogenous proviral sequences. 642 51

The noteworthy cytostatic activity of triglycidyl-s-triazinetrione and the planned clinical testing of this new active substance induced us to subject this class of substances to closer examination. By chemical reaction of one of the three glycidyl groups present it was possible to introduce wide variations in the properties of the compounds, whilst still retaining the active principle. A number of these substances possessed very high antitumor activity as revealed in the leukemia screening test (P 388; mouse). The influence of other substituents within the glycidyl groups affecting the reactivity of the epoxides groups was also examined.
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PMID:Investigation of the antitumor activity of new epoxide derivatives. Part I: s-Triazinetrione derivatives. 654 May 67

Liposomes have been used in recent years as carriers for drugs and molecules of biological importance. In cancer chemotherapy, however, the advantages of liposome encapsulation of antitumor drugs remain uncertain, with the possible exception of the usefulness of encapsulated 1-beta-D-arabinofuranosyl-cytosine (ara-C), an antitumor drug of a very short half-life. Liposome-encapsulated ara-C has been shown by others to enhance significantly the survival time of mice bearing leukemia, and the enhancement may be attributable to the role of liposomes as a slow release system for ara-C. We now further explore the advantages of two sustained release systems for ara-C, namely the liposome-encapsulated ara-C and 1-beta-D-arabinofuranosylcytosine-5'-diphosphate-L-1,2-dipalmitin (ara-CDP-L-dipalmitin, a prodrug of ara-C). Intravenously implanted Lewis lung carcinoma is used as a solid tumor model. The therapeutic effectiveness of the two slow release forms of ara-C given by either i.v. or i.p. injections is examined. Viable tumor cells (1.0 X 10(5) cells/mouse) were inoculated i.v. and treatment was initiated 24 hr later using three schedules of multiple treatments for liposomal ara-C and single or multiple injections of ara-CDP-L-dipalmitin. Liposomal ara-C given by the i.p. route consistently increased the number of cures (greater than 120 days survival). For example, when nine small doses (10 mg/kg) were given on consecutive days by i.p. injections, 50% of mice given liposomal ara-C were cured, compared with 10% cures in the group given ara-C liposomes by i.v. and no cures in mice receiving free ara-C given according to the same schedules. On the other hand, ara-CDP-L-dipalmitin given at a single dose is more effective than an equal dose divided in five injections. However, no cures have been obtained by treatments with ara-CDP-L-dipalmitin. These results have further demonstrated the advantage of liposomes as carriers for antitumor drugs of short half-life.
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PMID:The treatment of intravenously implanted Lewis lung carcinoma with two sustained release forms of 1-beta-D-arabinofuranosylcytosine. 654 Jun 91

Since increasing evidence indicates that combination modality of cancer treatment is preferable, and a series of 5-halo-6- phenylpyrimidinones has been found to induce interferon production and to stimulate a variety of immune responses, several were tested alone or in combination with cyclophosphamide (CY) against B 16 melanoma and P388 leukemia. Thus far, 2-amino-5-bromo-6-(3-fluorophenyl)-4(3H)pyrimidinone ( ABMFPP ) and its sister compound 2-amino-5-bromo-6-(2-fluorophenyl)-4(3H)pyrimidinone ( ABOFPP ) were found to be superior to other pyrimidinones including 2-amino-5-bromo-6-(6-phenyl)-4-pyrimidinone which is currently under clinical investigation. Neither ABMFPP nor ABOFPP alone had any significant activity against P388 leukemia. However, a marked synergistic effect was observed when a single i.p. injection of CY at 24 hr after tumor inoculation (10(6) cells/mouse) was followed by multiple i.p. injections of either ABMFPP or ABOFPP . For instance, the increase of life span was about 180% when animals received both CY (150 mg/kg) and ABMFPP (125 mg/kg/injection) as compared to 100% increased life span when animals received CY alone, and 0% increased life span when animals received ABMFPP alone. Also, 80% of the animals were long-term survivors (greater than 30 days) when animals received the combination therapy as compared to 20% survivors when animals received CY alone. The synergistic effect exhibited by ABMFPP or ABOFPP correlated positively to the initial reduction of tumor burden by CY. The optimal gap between CY and pyrimidinone administration was one day. The best therapeutic response was observed when pyrimidinone was given every 4 days for a total of 7 injections; however, other schedules and dosing frequencies also gave significant responses. The synergistic effect was also observed with B 16 melanoma when animals received the combination therapy. The significance of these findings, in terms of theoretical consideration as well as drug development, is discussed.
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PMID:Chemoimmunotherapy of B 16 melanoma and P388 leukemia with cyclophosphamide and pyrimidinones. 672 13

The effect of various natural pyrimidines and purines and their nucleosides and deoxynucleosides on 5-fluorouracil (FUra) cytotoxicity was examined against the transplantable AKR leukemia in female AKR mice. The spleen colony assay was used for a quantitative evaluation of the antitumor activity of the combination treatments. The base or nucleoside was administered 15 minutes before each mouse received an injection of 0.6 mg FUra. All of the compounds tested, with the exception of adenine, potentiated the cell-killing effect of FUra. On a molar basis (16-30 mumol/mouse), thymine, uracil, thymidine, and uridine enhanced FUra cytotoxicity more than a hundredfold. 2'-Deoxyuridine and the purine nucleosides and deoxynucleosides had similar potentiating activities between tenfold and fortyfold at 30 mumol per mouse. Finally, glucose, also administered 15 minutes before each mouse received an injection of 0.6 mg FUra, enhanced the antitumor activity of the drug by a factor of about five.
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PMID:In vivo potentiation of 5-fluorouracil cytotoxicity against AKR leukemia by purines, pyrimidines, and their nucleosides and deoxynucleosides. 692 48

The antitumor effect of dicyclohexylammonium sulfate (DCHA), a potent inhibitor of spermidine synthase, was tested on BDF1 mice inoculated i.p. with P388 leukemia (1 X 10(6) cells/mouse). DCHA prolonged the survival time of mice bearing P388 leukemia at the doses of 10-100 mg/kg administered daily for 6 days. The spleen weight increased by 30% at 7 days after tumor inoculation. DCHA treatment had no effect on the tumor-induced increase in splenic weight. The spermidine concentration of the ascites tumor cells and spleens of mice bearing the tumor was lowered by the treatment, while spermine concentration hardly changed. The depletion of spermidine in the ascites tumor cells and spleens might be a cause of the suppression of tumor growth.
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PMID:Antitumor effect of dicyclohexylammonium sulfate, a potent inhibitor of spermidine synthase against P388 leukemia. 711 28


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